Hearing loss is a significant problem with millions of Americans afflicted with some sort of hearing deficit. The primary targets of most agents that cause hearing loss are the cochlear hair cells. The loss of these specialized sensory receptors in mammals is permanent, however, chickens and other avian species are able to replace lost cochlear hair cells. This proposal has been designed to address prevention of cochlear hair cell death caused by gentamicin ototoxicity. The first set of experiments is designed to characterize what effect blocking different stages of the apoptotic cascade has on hair cell viability, and to determine if cochlear hair cell loss can be prevented in vitro. Once it is determined if gentamicin-induced cochlear hair cell death can be prevented in vitro, the second set of experiments investigates two in vivo methods of apoptosis inhibitor delivery to determine which one provides the best protection for cochlear hair cells. The data obtained here will provide important information regarding the prevention of cochlear hair cell death after gentamicin ototoxicity and the development of therapeutic tools that may help prevent hearing loss. [unreadable] [unreadable] [unreadable]